The overall objective of the proposed research is to conduct studies of the toxicology and disposition of prototype drugs in newborn and adult animals. The effects of hyperbilirubinemia on the disposition of drugs will be examined using the Gunn rat. Studies will include plasma clearance of ICG and BSP, competitive binding to hepatic Y protein and competitive binding to hepatic cell membranes. The role of bilirubin as an inducer of alternated patterns of bilirubin transport will be investigated in hepatectomized rats. Development studies on the gastrointestinal and subcutaneous absorption of drugs considered to be poorly absorbed will be made in newborn and adult animals using a pharmacokinetic model for bioavailability.